Prevalence of Malaria and Leptospirosis Co-Infection among Febrile Patients: A Systematic Review and Meta-Analysis

Abstract

Malaria and leptospirosis are important cosmopolitan infections that have emerged with overlapping geographic distribution, especially in tropical and subtropical regions. Therefore, co-infection with malaria and leptospirosis may occur in overlapping areas. The present study aimed to quantify the prevalence of malaria and leptospirosis co-infection among febrile patients. The association between malaria and leptospirosis infections was also investigated. Relevant studies that had reported malaria and leptospirosis co-infection were identified from PubMed, Scopus, and Web of Science. The risk of bias of the studies was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Tool. The pooled prevalence of malaria and leptospirosis co-infections among febrile patients and the pooled prevalence of leptospirosis infection among malaria patients were estimated using random effect models. The association between malaria and leptospirosis infection among febrile patients was estimated using random effect models. The outcomes of each study were shown in a forest plot in point estimate and 95% confidence interval (CI). Heterogeneity among the included studies was assessed using Cochran’s Q and quantified using I-squared statistics. For leptospirosis, subgroup analyses of countries, diagnostic tests, and participants’ age groups were performed to specify prevalence in each subgroup. Publication bias was assessed by funnel-plot visualization. Of the 2370 articles identified from the databases, 15 studies met the eligibility criteria and were included for qualitative and quantitative syntheses. Most of the included studies were conducted in India (5/15, 33.3%), Thailand (3/15, 20%), and Cambodia (2/15, 13.3%). Most of the enrolled cases were febrile patients (5838 cases) and malaria-positive patients (421 cases). The meta-analysis showed that the pooled prevalence of malaria and leptospirosis co-infection (86 cases) among febrile patients was 1% (95% CI: 1–2%, I2: 83.3%), while the pooled prevalence of leptospirosis infection (186 cases) among malaria patients was 13% (95% CI: 9–18%, I2: 90.3%). The meta-analysis showed that malaria and leptospirosis co-infections occurred by chance (p: 0.434, OR: 1.4, 95% CI: 0.6–3.28, I2: 85.2%). The prevalence of malaria in leptospirosis co-infection among febrile patients in the included studies was low. Co-infection was likely to occur by chance. However, as clinical symptoms of leptospirosis patients were non-specific and not distinguishable from symptoms of malaria patients, clinicians caring for febrile patients in an area where those two diseases are endemic should maintain a high index of suspicion for both diseases and whether mono-infections or co-infections are likely. Recognition of this co-infection may play an important role in reducing disease severity and treatment duration.

Prevalence and Characteristics of Malaria and Influenza Co-Infection in Febrile Patients: A Systematic Review and Meta-Analysis

“…In hypoendemic areas such as South-East Asia, malaria is frequently found in rural populations; hence, the first differential diagnosis of patients who present with fever after spending time in the forest is malaria rather than influenza. Co-infection of malaria with other AFIs was reported in our previous studies [27][28][29]. Co-infections patients were less reported, perhaps because of under-reporting or underevaluation or misdiagnosis.…”

“…Co-infections patients were less reported, perhaps because of under-reporting or underevaluation or misdiagnosis. Nevertheless, co-infection of malaria with leptospirosis or chikungunya tended to occur by chance [27,28]. Regarding malaria and influenza co-infection, the high prevalence of co-infection under poor living conditions might be associated with poor outcomes from influenza infection, especially in developing countries [30,31].…”

The diagnosis of leptospirosis complicated by pulmonary tuberculosis complemented by metagenomic next-generation sequencing: A case report

“…Cases of leptospirosis with other infectious comorbidities, such as dengue ( Wijesinghe et al., 2015 ; Paul, 2022 ), malaria ( Wilairatana et al., 2021 ), chikungunya ( Nhan et al., 2016 ; Cardona-Ospina et al., 2018 ), and scrub typhus ( Watt et al., 2003 ; Borkakoty et al., 2016 ; Vikram et al., 2020 ), have been increasingly described in tropical and subtropical regions, especially in the overlapping endemic regions. Co-occurrences of leptospirosis and tuberculosis in humans, however, are less frequently reported ( Viswanathan and Iqbal, 2015 ).…”

Distinct cytokine profiles in malaria coinfections: A systematic review

“…In malaria-endemic areas, malaria can coinfect with other tropical diseases as they have overlapping geographical distributions. Notably, several malaria coinfections with other tropical diseases have been documented, including dengue [ 17 ], hookworm [ 18 ], human African trypanosomiasis [ 19 ], typhoidal/nontyphoidal Salmonella [ 20 ], scrub typhus [ 21 ], visceral leishmaniasis [ 22 ], leptospirosis [ 23 ], Chikungunya [ 24 ], and the most recent coronavirus disease (COVID-19) or severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) [ 25 ]. Because malaria coinfections may lead to severe diseases, such as malaria–dengue [ 26 ], malaria–human African trypanosomiasis [ 19 ], or malaria–nontyphoidal Salmonella coinfections [ 20 ], studies on malaria coinfections are crucial for understanding the role of other diseases in malaria pathophysiology and clinical outcomes.…”